University of Connecticut, School of Pharmacy, Storrs, CT 06269, USA.
AbbVie Pte Ltd, Research and Development, 11 Biopolis Way, Helios, #05-06, Singapore 138667, Singapore.
Int J Pharm. 2014 Apr 10;464(1-2):234-42. doi: 10.1016/j.ijpharm.2013.12.039. Epub 2014 Jan 9.
Quality by Design (QbD) principles were explored to understand spray drying process for the conversion of liquid nanosuspensions into solid nano-crystalline dry powders using indomethacin as a model drug. The effects of critical process variables: inlet temperature, flow and aspiration rates on critical quality attributes (CQAs): particle size, moisture content, percent yield and crystallinity were investigated employing a full factorial design. A central cubic design was employed to generate the response surface for particle size and percent yield. Multiple linear regression analysis and ANOVA were employed to identify and estimate the effect of critical parameters, establish their relationship with CQAs, create design space and model the spray drying process. Inlet temperature was identified as the only significant factor (p value <0.05) to affect dry powder particle size. Higher inlet temperatures caused drug surface melting and hence aggregation of the dried nano-crystalline powders. Aspiration and flow rates were identified as significant factors affecting yield (p value <0.05). Higher yields were obtained at higher aspiration and lower flow rates. All formulations had less than 3% (w/w) moisture content. Formulations dried at higher inlet temperatures had lower moisture compared to those dried at lower inlet temperatures.
质量源于设计（QbD）原则被探索用于理解喷雾干燥过程，将液体纳米混悬液转化为固体纳米结晶干粉末，使用吲哚美辛作为模型药物。使用全因子设计研究了关键工艺变量：入口温度、流速和吸气率对关键质量属性（CQAs）的影响：粒径、水分含量、产率和结晶度。采用中心立方设计生成粒径和产率的响应面。采用多元线性回归分析和方差分析来识别和估计关键参数的影响，建立它们与 CQAs 的关系，创建设计空间并对喷雾干燥过程进行建模。入口温度被确定为唯一显著影响干粉粒径的因素（p 值<0.05）。较高的入口温度导致药物表面熔化，从而导致干燥纳米结晶粉末聚集。吸气率和流速被确定为影响产率的重要因素（p 值<0.05）。在较高的吸气率和较低的流速下获得较高的产率。所有配方的水分含量均小于 3%（w/w）。在较高入口温度下干燥的配方比在较低入口温度下干燥的配方具有更低的水分含量。
